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BACKGROUND/AIMS: Gain-of-function mutations in exons 9, 11 and 13 of the c-kit gene in gastrointestinal stromal tumors (GISTs) have been identified, and it has been reported that the prognosis is worse for patients with mutation-positive GISTs than for those with mutation-negative GISTs. We studied c-kit mutations in gastrointestinal mesenchymal tumors. By chance, the c-kit mutation in exon 11 was found in myogenic and neurogenic tumors as well as in GISTs. Furthermore, we studied the clinical prognostic utility of these mutations. METHODS: Ten gastrointestinal mesenchymal tumors were stained with HE and immunohistochemically analyzed with alpha-smooth muscle actin, S-100 protein, CD34 and c-kit. In these tumors, as well as in 11 cases of leiomyomas, PCR-amplified DNA from the juxtamembrane (JM) domain of exon 11, the extracellular domain of exon 9 and the tyrosine kinase domain 1 of exon 13 showed a high frequency of c-kit mutation and was sequenced. RESULTS: Although c-kit mutations have previously been reported only in GISTs, we found c-kit mutations in the JM domain of exon 11 in one myogenic and one neurogenic tumor as well as in two GISTs. No c-kit mutation was seen in the 11 cases of leiomyomas. In addition, all four cases with c-kit mutation in exon 11 suffered a relapse sooner than the other cases without c-kit mutations. CONCLUSION: Clinically, the prognosis was worse for the patients with mutation-positive gastrointestinal mesenchymal tumors than for those with mutation-negative tumors. We therefore conclude that the gain-of-function mutation in exon 11 of the c-kit gene is an important prognostic factor for gastrointestinal mesenchymal tumors, including myogenic and neurogenic tumors as well as GISTs.
Benign and malignant neural and neuroendocrine tumors of the larynx are uncommon enough that knowledge about them is sparse, coming from single case reports and literature reviews. We have reviewed the clinical behavior, pathologic findings, treatment, and outcome in 42 patients seen at one institution from 1907 to 1986. In some cases, electron microscopy or immunocytochemistry, or both, may be needed to reach the correct diagnosis. Treatment is largely determined by the histopathologic features, size, and location of the tumor. The most common sites are the supraglottic region and posterior larynx. Most tumors are treated by conservation surgery, including transoral excision; however, some are aggressive and require larger surgical procedures, including wide-field laryngectomy and complete neck dissection.
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GIST have still today controversial aspects of their histogenesis that are reflected on the classification and prognosis. It's showed a particular case with mixed muscular-neuronal histogenesis that supposes totipotent cell origin of these neoplasms. Diagnosis, classification and prognosis are very difficult to evaluate; surgery at the moment is the only useful treatment modality.
A case of intravenous leiomyomatosis with cardiac extension was treated successfully with a two-stage operation: resection of the intracardiac and intracaval mass for the first stage and total hysterectomy with bilateral salpingo-oophorectomy for the second. Tumors were located either within or in continuity to dilated uterine veins. A leiomyomatous protrusion of the wall of a small uterine vein was found in two remote sections. The involved veins were located alone in the layer of apparently normal uterine smooth muscles. The findings suggest that intravenous leiomyomatosis originates from the smooth-muscle component of uterine veins.
Three cases of granular cell myoblastoma have been studied in order to determine the presence and distribution of the S-100 specific protein in the neoplastic cells, using immunocytochemical staining techniques, through the modified avidin-biotin method. Positive immunostaining was observed in the three cases studied. The comparative study of various control cases histogenetically originating from neuroectoderm (melanoma) and specifically from Schwann cells, as also the presence of strongly positive staining in Schwann cells of peripheral nerve fibres situated inside and outside the tumor, support the concept of the neurogenic origin of this interesting tumor.
The clinical presentations of various nonsquamous tumors of the oral cavity are reviewed, along with their gross pathology, histology, and treatment. Survival rates are presented for those neoplasms that occur frequently enough to allow meaningful analysis of various modes of therapy.
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